Herpesviruses are enveloped double stranded DNA-containing viruses in an icosahedral nucleocapsid. At least seven herpesviruses are associated with infection in humans, including herpes simplex virus type-1 (HSV-1), herpes simplex virus type-2 (HSV-2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7).
HSV-1 is one of the most intensively studied herpesviruses. HSV-1 exhibits a pattern of gene expression during productive infection which is stringently regulated (Fields et al. Virology, 1990, Raven Press, NY). The more than 70 genes identified in this virus are classified in part according to the kinetics of their expression. Expression of each class of genes is dependent upon expression of genes from the preceding class. The viral immediate early, or α, genes are expressed first, followed by the viral early, or β, genes which in turn are followed by the late, or γ, genes. The γ genes are further subdivided into γ-1 and γ-2 genes, depending upon the extent to which their expression relies upon viral DNA replication.
Several viral proteins have been shown to regulate expression of HSV-1 genes. The ICP4 protein is essential for β and γ gene expression (DeLuca et al., J. Virol., 56:558 (1985)). The ICP27 protein is required for γ gene expression and for viral DNA replication (McCarthy et al., J. Virol., 63:18 (1989)). The major DNA-binding protein (ICP8), a β gene product, is also required for viral DNA replication and for γ gene expression (Gao et al., J. Virol. 63:5258 (1989); Quinlan et al., Cell, 36:657 (1984)).
Diseases caused by herpesviruses in humans vary from mild to severe, and in some cases, infection with these viruses is life-threatening.
Vaccination is a common approach to prevention of disease. Various vaccines based on isolated immunogens, and on live, attenuated virus have been proposed for herpesviruses (Roizman, U.S. Pat. No. 4,859,587; and Meignier et al., J. Inf. Dis., 3:603-613 (1988) (HSV); Takahasi et al., Biken J., 18:25-33 (1975) (VZV); Elek et al., Lancet, 1:1-5 (1974); and Plotkin et al. Infect. Immun, 12:521-527 (1975) (CMV)).
Further, development of therapeutic immunomodulants for treating immunopathologic diseases, such as herpetic stromal keratitis, would be desirable (Jayaraman et al., J. of Immunology, 151:5777-5789, Nov. 15, 1993).